The overall objective of this project is to better understand selective cellular and subcellular aspects of adaptive immune responses. The proposed studies are focused on the channel catfish, a teleost representing the economically most important freshwater aquaculture species in the USA. The specific aims are four. The first will be focused on catfish B-cells and will include structural and functional assessments of Ig-associated accessory molecules and the newly discovered catfish homolog of the IgD heavy chain. The second will be focused on catfish T-cells and will include structural and functional assessments of catfish T-cell receptors and Il-1 receptors. The third will involve characterizing a population of newly discovered catfish cytotoxic cells with a view to determining if they are the fish homologs of T cytotoxic cells (CTL) with reactivity for MHC molecules or a novel type of NK cells. Finally, attempts will be undertaken to define the mechanism(s) whereby catfish peripheral blood leukocytes can be readily "immortalized" to functionally active long-term diploid cell lines without apparent transformation maneuvers, restimulation or exogenous factors; emphasis will be devoted to ascertaining the roles of telomerase, heat shock proteins, tumor suppressors and oncogene products. At the present time the channel catfish represents the only teleost wherein numerous different interrelated in vitro functional and molecular biological assessments can be readily conducted in the context of a variety of contemporary immunological issues. Hence this species must be considered as an important "lower vertebrate" model system for studying adaptive immunity. It seems likely that completion of these proposed studies will yield important novel and definitive information regarding both basic and applied aspects of immune phylogeny.